Therapeutic and Mechanistic Perspectives of Protein Complexes in Breast Cancer.

Breast cancer affects one in eight women making it the most common cancer in the United Kingdom, accounting for 15% of all new cancer cases. One of the main challenges in treating breast cancer is the heterogeneous nature of the disease. At present, targeted therapies are available for hormone receptor- and HER2-positive tumors. However, no targeted therapies are currently available for patients with triple negative breast cancer (TNBC). This likely contributes to the poor prognostic outcome for TNBC patients. Consequently, there is a clear clinical need for the development of novel drugs that efficiently target TNBC. Extensive genomic and transcriptomic characterization of TNBC has in recent years identified a plethora of putative oncogenes. However, these driver oncogenes are often critical in other cell types and/or transcription factors making them very difficult to target directly. Therefore, other approaches may be required for developing novel therapeutics that fully exploit the specific functions of TNBC oncogenes in tumor cells. Here, we will argue that more research is needed to identify the protein-protein interactions of TNBC oncogenes as a means for (a) mechanistically understanding the biological function of these oncogenes in TNBC and (b) providing novel therapeutic targets that can be exploited for selectively inhibiting the oncogenic roles of TNBC oncogenes in cancer cells, whilst sparing normal healthy cells

Droplet Spreading Process Impact on Ignition Characteristics of Condensed Materials

Mathematical simulation of condensed material solid-phase ignition in the context of the in-situ heating by the melted or heated to high temperature metal droplet was carried out. The authors developed the mathematical model that describes the heat transfer process in the "droplet – condensed material" system by the system of heat transfer equations with boundary and initial conditions. The problem is solved by the finite difference method. Four modes of condensed material ignition that are distinguished by the temperature range of every mode were identified for standard conditions of the in-situ heat effect

Two-dimensional maps at the edge of chaos: Numerical results for the Henon map

The mixing properties (or sensitivity to initial conditions) of two-dimensional Henon map have been explored numerically at the edge of chaos. Three independent methods, which have been developed and used so far for the one-dimensional maps, have been used to accomplish this task. These methods are (i)measure of the divergence of initially nearby orbits, (ii)analysis of the multifractal spectrum and (iii)computation of nonextensive entropy increase rates. The obtained results strongly agree with those of the one-dimensional cases and constitute the first verification of this scenario in two-dimensional maps. This obviously makes the idea of weak chaos even more robust.Comment: 4 pages, 3 figure

Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice

The aim of this work was to study the antifibrotic effect of pulmonary administration of tilorone to lung fibrosis. L-leucine coated tilorone particles were prepared and their aerosolization properties were analyzed using two dry powder inhalers (Easyhaler and Twister). In addition, the biological activity and cell monolayer permeation was tested. The antifibrotic effect of tilorone delivered by oropharyngeal aspiration was studied in vivo using a silica-induced model of pulmonary fibrosis in mice in a preventive setting. When delivered from the Easyhaler in an inhalation simulator, the emitted dose and fine particle fraction were independent from the pressure applied and showed dose repeatability. However, with Twister the aerosolization was pressure-dependent indicating poor compatibility between the device and the formulation. The formulation showed more consistent permeation through a differentiated Calu-3 cell monolayer compared to pristine tilorone. Tilorone decreased the histological fibrosis score in vivo in systemic and local administration, but only systemic administration decreased the mRNA expression of type I collagen. The difference was hypothesized to result from 40-fold higher drug concentration in tissue samples in the systemic administration group. These results show that tilorone can be formulated as inhalable dry powder and has potential as an oral and inhalable antifibrotic drug.Peer reviewe

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Mini nutritional assessment scale-short form can be useful for frailty screening in older adults

Aim: Mini Nutritional Assessment-Short Form (MNA-SF) is used to assess nutritional status in older adults, but it is not known whether it can define frailty. It was aimed to investigate that the MNA-SF can identify frailty status defined by Fried criteria. Methods: 1003 outpatients aged 65 or older were included the study. All patients were performed comprehensive geriatric assessment. Frailty status was evaluated by Fried criteria: unintentional weight loss, exhaustion, low levels of activity, weakness and slowness. 1 point is assigned for each criterion: 0 points, not frail; 1-2 points, prefrail; ≥3 points, frail. If the total score of MNA-SF was 11, it was accepted that there was malnutrition, risk of malnutrition, and no malnutrition, respectively. Results: Of the 1003 outpatients, of whom the mean age was 74.2 ± 8.5 years, 313 participants (31.2%) were considered frail and 382 (38.1%) pre-frail. Among frail patients and pre-frail patients, 49.2 and 25.1% were at risk of malnutrition and 22.0% and 1.6% were malnourished, respectively. MNA-SF with a cut-off point of 11.0 had a sensitivity of 71.2% and a specificity of 92.8% to detect frail participants, and with a cut-off point of 13 had a sensitivity of 45.7% and a specificity of 78.3% to detect pre-frailty. The area under the curve of MNA-SF was 0.906 and 0.687 for the estimation of frailty and pre-frailty, respectively. Conclusion: MNA-SF can be useful for frailty screening in older adults